title: Serum uric acid distribution according to SLC22A12 W258X genotype in a cross-sectional study of a general Japanese population.
abstract: BACKGROUND
  Although SLC22A12 258X allele was found among those with hypouricemia, it was unknown that serum uric acid distribution among those with SLC22A12 258X allele. This study examined serum uric acid (SUA) distribution according to SLC22A12 W258X genotype in a general Japanese population.
  
  
  METHODS
  Subjects were 5,023 health checkup examinees (3,413 males and 1,610 females) aged 35 to 69 years with creatinine <2.0 mg/dL, who were participants of a cohort study belonging to the Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study). SLC22A12 W258X was genotyped with a polymerase chain reaction with confronting two-pair primers.
  
  
  RESULTS
  The genotype frequency was 4,793 for WW, 225 for WX, and 5 for XX, which was in Hardy-Weinberg equilibrium (p=0.164) with X allele 0.023 (95% confidence interval [0.021-0.027]). Mean (range) SUA was 6.2 (2.1-11.4) mg/dL for WW, 3.9 (0.8-7.8) mg/dL for WX, and 0.8 (0.7-0.9) mg/dL for XX among males, and 4.5 (1.9-8.9) mg/dL, 3.3 (2.0-6.5) mg/dL, and 0.60 (0.5-0.7) mg/dL among females, respectively. Six individuals with SUA less than 1.0 mg/dL included two males with XX genotype, one male with WX genotype, and three females with XX genotype. Subjects with WX genotype were 14 (77.8%) of 18 males with a SUA of 1.0-2.9 mg/dL, and 28 (34.6%) of 81 females with the same range of SUA. The corresponding values were 131 (25.1%) of 522 males and 37 (3.5%) of 1,073 females for SUA 3.0-4.9 mg/dL, and 8 (0.4%) of 2,069 males and 5 (1.1%) of 429 females for SUA 5.0-6.9 mg/dL. The X allele effect for SUA less than 3 mg/dL was significantly (p<0.001) higher in males (OR=102.5, [33.9-309.8]) than in females (OR = 25.6 [14.4-45.3]).
  
  
  CONCLUSIONS
  Although SLC22A12 W258X was a determining genetic factor on SUA, SUA of those with WX genotype distributed widely from 0.8 mg/dL to 7.8 mg/dL. It indicated that other genetic traits and/or lifestyle affected SUA of those with WX genotype, as well as those with WW genotype.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. nhamajim@med.nagoya-u.ac.jp
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Yatami
authors.initials: Y
authors.lastname: Asai
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics*; D027701:Organic Cation Transport Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D014527:Uric Acid / Q000097:blood*
chemical_list: D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid; D003404:Creatinine